艾滋病抗病毒治疗乳酸酸中毒及高乳酸血症32例临床分析

乳酸酸中毒和高乳酸血症被认为是核苷类反转录酶抑制剂（NRTI）引起的严重甚或致命的远期副作用。广西壮族自治区疾病预防控制中心（CDC）门诊收治32例艾滋病（AIDS）抗病毒治疗乳酸酸中毒及高乳酸血症病人,现将其临床表现、诊疗经过及预后总结报告如下。     

替比夫定相关性肌病乳酸中毒1例报告

<正>乳酸性酸中毒和严重的肝脏脂肪变性是核苷(酸)类似物(NRTIs)等抗逆转录病毒类药物罕见的严重并发症之一[1],国内外文献报道[2]多见于高效抗逆转录病毒治疗(HAART)方案用于抗艾滋病病毒(HIV)感染治疗过程中。     

HAART相关症状性高乳酸血症的临床特征及影响因素分析

目的初步研究中国艾滋病患者高效抗逆转录病毒治疗（HAART）过程中发生的症状性高乳酸血症的临床特征及相关影响因素。方法对北京地坛医院2005年1月至2007年12月,所有接受HAART的患者每1—2月进行临床随访,共发现8例症状性高乳酸血症患者,对其治疗前后的免疫状况、治疗方案、高乳酸血症的临床表现、实验室检测结果,以及临床处理和预后进行综合分析。结果所有8例症状性高乳酸血症患者,均在发病前服用过含有司他夫定的HAART方案9—24个月,临床症状以自觉疲乏、恶心、腹部胀痛、肌肉酸痛、运动后呼吸困难为多见,血乳酸水平3．4—10．0mmol／L。5例未出现乳酸酸中毒的症状性高乳酸血症患者,经换药或停药并对症处理后均好转;3例发展为乳酸酸中毒,病情严重,其中1例死亡。结论引起高乳酸血症的原因较多,司他夫定可能是主要因素。     

23例HIV/AIDS病人HAART致乳酸酸中毒临床分析

目的探讨艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人在高效抗反转录病毒治疗(HAART)过程中,出现乳酸酸中毒的情况,其临床表现、诊断、治疗和预后,以进一步采取预防措施,降低其发生率和致死率。方法采用回顾性分析的方法,分析HAART时间及不同方案发生乳酸酸中毒的情况。结果 2010年1月-2011年8月收治的住院病人中,已经进行HAART的共1 115例,出现高乳酸血症者74例,占6.64%;发生乳酸酸中毒的病人23例,发生率2.06%。所有发生乳酸酸中毒的病人都采用含司他夫定(D4T)的方案。经过综合治疗的18例治愈,死亡5例,总死亡率21.74%(5/23)。HAART 6个月以上及应用含D4T方案的病人发生率最高,为4.41%(23/521)。结论乳酸酸中毒的发生率虽低,致死率高,且临床表现多不典型,易被误诊、漏诊;危险因素包括肥胖、女性、合并HCV应用干扰素利巴韦林治疗的病人、以及同时合并其他机会性感染病人等。     

核苷类逆转录酶抑制剂联合用药可使线粒体毒性持续性增加

一些核苷类逆转录酶抑制剂由于抑制了γ多聚酶,可引起肝脏线粒体(mt)DNA的缺失,后者可造成乳酸酸中毒、脂肪肝和肝衰竭。作者研究旨在评估核苷类逆转录酶抑制剂联合疗法的持续性线粒体毒性。     

早期乳酸清除率对重症社区获得性肺炎合并高乳酸血症患者预后的评估作用

目的研究早期乳酸清除率对重症社区获得性肺炎合并高乳酸血症患者预后的评估作用。方法回顾性分析58例重症社区获得性肺炎合并高乳酸血症患者,计算患者开始治疗24小时后的乳酸清除率,PSI及CURB-65评分变化率,将研究对象分别分为存活组与死亡组、高乳酸清除率组与低乳酸清除率组。比较存活组与死亡组之间的起始乳酸浓度、治疗24小时后乳酸清除率及PSI和CURB-65评分变化率并比较高乳酸清除率组与低乳酸清除率组治疗24小时后的死亡率、休克发生率和呼衰发生率有无差异。结果存活组与死亡组的起始乳酸浓度、PSI评分变化率差异无统计学意义,乳酸清除率及CURB-65变化率存活组明显高于死亡组;高乳酸清除率组治疗24小时后的死亡率、休克发生率和呼衰发生率明显低于低乳酸清除率组。结论治疗24小时后的乳酸清除率是评价重症社区获得性肺炎合并高乳酸血症患者病情严重程度、治疗效果和判断预后的重要指标之一。     

糖尿病并发乳酸性酸中毒

糖尿病并发乳酸性酸中毒上海铁道大学附属铁路医院上海２０００７２吴增常糖尿病并发乳酸性酸中毒随医学进展而显著减少，一旦发生本症，则病情极为危险。有肝、肾功能不全的患者易发生，常由休克或服用双胍类药物而诱发。本症血乳酸增高，严重酸中毒，一般并无高酮血症，...     

线粒体基因突变与MELAS综合征

线粒体脑肌病伴高乳酸血症和卒中样发作(mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes,MELAS)是线粒体脑肌病中     

糖尿病乳酸性酸中毒

乳酸性酸中毒是高阴离子间隙性酸中毒,由大量乳酸在体内堆积所致。血浆乳酸浓度取决于糖酵解及乳酸被利用速度,因各种原因致组织缺氧,乳酸生成过多,或因肝脏疾病使乳酸利用减少和清除障碍,则血乳酸浓度升高。正常人休息状态下静脉血乳酸含量为0.5~1.6mmol/L。当血乳酸浓度>2mmol/L(有人认为5mmol/L)时可产生乳酸性酸中毒。若血乳酸浓度升高,但动脉血pH仍在正常范围,称之为高乳酸血症;若血乳酸浓度升高,动脉血pH失代偿而低于7.35,称之为乳酸性酸中毒。在糖尿病基础上发生的乳酸性酸中毒称之为糖尿病乳酸性酸中毒,它是糖尿病的三大急性并发…     

高效抗反转录病毒治疗相关性脂肪代谢综合征

自1996年高效抗反转录病毒治疗(HAART)应用于临床以来,艾滋病的发病率和死亡率已经大大降低。但HAART治疗需长期或终身服药,因此,药物的毒副作用容易导致患者的依从性下降。其中脂肪代谢综合征就是HAART用药过程中的一个比较常见的远期不良反应之一。HAART药物中与脂肪代谢有关的主要是蛋白酶抑制剂(PIs)和核苷类逆转录酶抑制剂(NRTIs),可以引起各种代谢异常和内分泌紊乱综合征。其具体的发病机制目前尚不清楚。本文就脂肪代谢综合征的发病机制、检测及治疗进行了阐述。     

高效抗逆转录病毒疗法对机会性致病原虫的作用

机会性致病原虫在HIV感染者中是最重要的致病与致死的原因之一。自20世纪后期高效抗逆转录病毒疗法(HAART)问世后,机会性致病寄生虫的感染率明显下降。非核苷类逆转录酶抑制剂、HIV蛋白酶抑制剂及核苷类逆转录酶抑制剂这3类药物中,至少2种联合应用的HAART,对细胞免疫的下降有恢复作用,也有证据表明HIV蛋白酶抑制剂对寄生虫的蛋白酶有直接抑制作用。     

Phosphorylation of thymidine and AZT in heart mitochondria

Antiretroviral nucleoside analogs used in highly active antiretroviral therapy (HAART) are associated with cardiovascular and other tissue toxicity associated with mitochondrial DNA depletion, suggesting a block in mitochondrial (mt)-DNA replication. Because the triphosphate forms of these analogs variably inhibit mt-DNA polymerase this enzyme has been promoted as the major target of toxicity associated with HAART. We have used isolated mitochondria from rat heart to study the mitochondrial transport and phosphorylation of thymidine and AZT (azidothymidine, or zidovudine), a component used in HAART. We demonstrate that isolated mitochondria readity transport thymidine and phosphorylate it to thymidine 5′-triphosphate (TTP) within the matrix. Under identical conditions, AZT is phosphorylated only to AZT-5′-monophosphate (AZT-MP). The kinetics of thymidine and AZT agest negative cooperatively of substrate interaction with the enzyme, consistent with work by others on mitochondrial thymidine kinase 2. Results show that TMP and AZT-MP are not transported across the inner membrane, suggesting that AZT-MP may accumulate with time in the matrix. Given the lack of AZT-5′-triphosphate (AZT-TP), it seems unlikely that the toxicity of AZT in the heart is mediated by AZT-TP inhibition of DNA polymerase γ. Rather, our work shows that AZT is a potent inhibitor of thymidine phosphorylation in heart mitochondria, having an inhibitory concentration (IC)₅₀ of 7.0±0.9 μM. Thus, the toxicity of AZT in some tissues may be mediated by disrupting the substrate supply of TTP for mt-DNA replication.     

Long‐term therapy for chronic hepatitis B: Hepatitis B virus DNA suppression leading to cirrhosis reversal

Since the licensing of the first treatment for chronic hepatitis B in the nucleoside/tide analog class almost 15 years ago, considerable progress has been made in improving drug efficacy and safety with highly potent nucleoside/tide analogs exhibiting a high barrier to resistance. Physicians are now able to treat patients safely for many years and to be able to see convincing improvements in histology, including regression of fibrosis and even reversal of cirrhosis. The robust data that have been generated help us build confidence that we can now offer patients with chronic hepatitis B long‐term, disease‐modifying therapy that can alter the natural course of disease and help prevent the morbidity and mortality associated with it.     

Nucleoside analogues resistance in the treatment of chronic hepatitis B virus infection

SUBJECT: Chronic hepatitis B virus (HBV) infection is usually treated by interferon alpha. However, a sustained response after stopping treatment is only obtained in 30% of patients. ACTUALITY: New therapeutic nucleoside analogs have been developed, i.e. lamivudine, famciclovir, adefovir, entecavir, clevudine. However, as in HIV infection, clearance of the original hepatitis B virus with emergence of distinct resistant mutants have been observed during or after treatment with most nucleoside analogs. In this review, the underlying mechanisms of resistance and the characterisation of HBV mutants are described to optimize the best therapeutic regimen. PERSPECTIVES: Treatment of chronic HBV infection, as most of other chronic viral infection, should be based on combination therapy with a special search for the appearance of HBV mutant resistant.     

Infectious lung complications in patients with HIV/AIDS

PURPOSE OF REVIEW: The aim of this article is to review recent observations in the area of infectious lung complications in individuals with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Since the immunodeficiency was first characterized, it has been associated with enhanced susceptibility to opportunistic infection, and life-threatening infections of the lung in particular. In the past few years there have been a large number of reports documenting the changes to this disease profile in the age of highly active antiretroviral therapy (HAART). Furthermore, there have been considerable advances in our understanding of the immunology and vaccinology of many of the pathogens implicated in pulmonary infections in this context, including Mycobacterium tuberculosis, Streptococcus pneumoniae and Pneumocystis pneumonia. RECENT FINDINGS: In considering the time-course and spectrum of HIV-associated respiratory infections, the field must now be divided into studies undertaken in parts of the world where HAART is accessible and those where it is not. Despite the enormous impact of HAART, it has brought with it a new set of concerns, including the effects of immune restoration disease (IRD), and the complex interplay between HAART and tuberculosis therapy. SUMMARY: The overriding conclusion from recent experience is that HAART, in those parts of the world where it is readily available, has changed the clinical picture of infections associated with HIV, and needs to be available to patients across the developing world as well. Furthermore there have been important developments in vaccination programs against pathogens involved in HIV-associated pneumonia.     

Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection

In two of 15 patients coinfected with HIV and hepatitis C virus who received interferon-alpha plus ribavirin in addition to HAART, we observed multiorgan dysfunction and lactic acidaemia. As ribavirin is a nucleoside analogue, an increased risk of mitochondrial toxicity can be induced in HIV-infected patients already treated with nucleoside analogues, leading to clinical deterioration in some cases.